2. Academic Validation
  3. Monomethyl branched-chain fatty acid mediates amino acid sensing upstream of mTORC1

Monomethyl branched-chain fatty acid mediates amino acid sensing upstream of mTORC1

  • Dev Cell. 2021 Oct 11;56(19):2692-2702.e5. doi: 10.1016/j.devcel.2021.09.010.
Mengnan Zhu 1,  Fukang Teng 2,  Na Li 3,  Li Zhang 2,  Shuxian Zhang 2,  Fan Xu 2,  Jing Shao 4,  Haipeng Sun 4,  Huanhu Zhu 5
Affiliations

Affiliations

  • 1 School of Life Science and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • 3 School of Life Science and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
  • 4 National Humanities Center Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Center for Cardiovascular Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
  • 5 School of Life Science and Technology, ShanghaiTech University, Shanghai, China. Electronic address: zhuhh1@shanghaitech.edu.cn.
PMID: 34610328 DOI: 10.1016/j.devcel.2021.09.010
Abstract

Animals have developed various nutrient-sensing mechanisms for survival under fluctuating environmental conditions. Although extensive cell-culture-based analyses have identified diverse mediators of amino acid sensing upstream of mTOR, studies using animal models to examine intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here, we developed a Caenorhabditis elegans model to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid and its downstream metabolite, glycosphingolipid, which critically mediates the overall amino acid sensing by intestinal and neuronal mTORC1, which in turn regulates postembryonic development at least partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may operate in mammals. This study uncovers an amino-acid-sensing mechanism mediated by a lipid biosynthesis pathway.

Keywords

C. elegans; amino acid sensing; developmental arrest; developmental control; glucosylceramide; mTOR; mTORC1; mmBCFA; nutrient sensing; sphingolipid.

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